Metasyn, Inc. is developing targeted relaxation agents for magnetic resonance imaging (MRI) of the liver. These agents will be used to enhance the detection of cancer which has spread to the liver from distant sites. The agents are in the form of gadolinium(III)-containing complexes that are taken up by hepatocytes and bind to cytosolic proteins. The binding to proteins increases the relaxation ability of the agents, yielding high MRI enhancement at low doses. The overall goals of the project are to demonstrate the feasibility of certain gadolinium(III) diethylenetriaminepentaacetate [Gc(DTPA)2-] derivatives with one or more aryl ring substituents and determine structure-activity relationships (SAR) to aid in compound selection. The specific aims of the proposed research are: 1. To determine the importance of overall lipophilicity and the number and orientation of aryl groups attached to the chelates in governing hepatocellular uptake (in isolated rat hepatocytes) and relaxivity. 2. To analyze the SAR for hepatocellular uptake and relaxivity and select a basic framework for the agent. 3. To confirm the performance of selected agents in in vivo biodistribution and MRI studies in rats. 4. To synthesize and test additional derivatives of the selected framework. 5. To select two to four optimal prototype compounds for further development. In Phase II of this SBIR project, we will evaluate the compounds in dose dependence, uptake inhibition, and formal pharmacology/toxicology studies as well as Phase I clinical trials.